The effects of IL-1A and IL-6 genes polymorphisms on gene expressions, hormonal and biochemical parameters in polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is a multifactorial disease characterised by chronic inflammation. We aimed to investigate an association between IL-1A and IL-6 gene polymorphisms and both hormonal/biochemical parameters and levels of IL-1A and IL-6. A total of 103 women diagnosed with PCOS according to ESHRE/ASRM criteria were investigated. The patients were divided into two groups as obese and non-obese. IL-1A and IL-6 genes polymorphisms as well as hormonal/biochemical parameters and levels of IL-1A and IL-6 were analysed in the same groups. Serum IL-1A and IL-6 levels were found to increase both in obese and non-obese groups. However, there was no association between IL-1A level and IL-1A polymorphism. A relationship was detected between H score, FSH, LH, total testosterone, HDL-C and TG levels and CG + GG genotypes of IL-6. Furthermore, an association was found between IL-6 levels and CC genotype of IL-6 in the obese PCOS patients. The abnormalities in hormonal/biochemical parameters detected in Turkish PCOS patients may be related with IL-6 gene polymorphism rather than IL-1A.

The Effects of Polymorphisms of Death Pathway Genes and Mitochondrial Pathway Genes in Intervertebral Disc Degeneration.

AIM: It has been proposed that apoptosis is effective on intervertebral disc degeneration. This study is the first study in which both polymorphisms and expressions of apoptotic genes in patients with intervertebral disc degeneration (IVDD) are evaluated together. The aim of our study is to determine whether polymorphisms and expressions of apoptotic genes involved in both pathways are related with grades of IVDD or not. MATERIAL AND METHODS: Blood and tissue samples of 100 patients diagnosed with lumbar disc degeneration were collected. Patients were divided into 2 groups according to their radiological degeneration grades; grade 2 (mild), and grade 3 and 4 (severe). Polymorphisms in Fas (rs 2234767), Bcl-2 (rs 1801018) and Bax (rs 4645878) genes were determined with real-time PCR. Expressions of these genes were analyzed immunohistochemically following histological degeneration scoring. RESULTS: Whereas no relationship was found among polymorphisms of Fas and Bax genes and their expressions, we have determined a relationship among GG genotype of Bcl-2 and their expressions. Additionally, the ratio of Bax-positive cells was related with IVDD grades. Moreover, radiological degeneration grades were compatible with histological degeneration scores. CONCLUSION: GG genotype of Bcl-2 gene may influence the level of its expression and may be effective on the development of IVDD. Additionally, expression of Bax gene may be related with different grades of IVDD.

Evaluation of tool-like receptor-2 and 4 and interleukin-6 gene expressions in Turkish rheumatoid arthritis patients.

Rheumatoid arthritis (RA) is a progressive inflammatory disease. Although the etiology and pathogenesis of RA are not known well, genetic and environmental factors are proposed to initiate an autoimmune process. We aimed to investigate mRNA expression levels of Toll-like receptor-2 (TLR-2), TLR-4, and interleukin-6 (IL-6) genes in RA disease. This study was conducted with 50 patients who were diagnosed with RA according to the American College of Rheumatology classification criteria for RA and 50 age-matched healthy control individuals who did not have any joint diseases and autoimmune diseases. We collected whole blood from all participants and analyzed expression of TLR-2, TLR-4, and IL-6 genes at mRNA level using real-time qPCR. TLR-2 expression was detected to increase 3.8-fold and IL-6 expression was detected to increase 6.8-fold in RA patients compared to healthy controls. No difference was found between patient and control groups with regard to TLR-4 expression. Overexpression of TLR-2 and IL-6 may be responsible for RA pathogenesis. Inhibition of both TLR and IL signaling pathways may prevent joint inflammation and destruction.

NUCB2 gene polymorphism and its relationship with nesfatin-1 levels in polycystic ovary syndrome.

Nesfatin-1, encoded by the nucleobindin-2 (NUCB2) gene, is an anorexigenic protein related to energy metabolism, obesity, and insulin resistance. The aim of this study was to evaluate NUCB2 gene polymorphism (rs757081) and its association with serum levels of nesfatin-1 in obese and non-obese women with polycystic ovary syndrome (PCOS). In the study population, we analyzed 60 patients with PCOS and 26 age-matched healthy women as controls. The patients with PCOS were divided into two groups based on body mass index (BMI): obese group (n = 28) or non-obese group (n = 32). NUCB2 was genotyped using the polymerase chain reaction-restriction (PCR) technique. Serum nesfatin-1 level was measured by enzyme-linked immunosorbent assay (ELISA). Nesfatin-1 levels in the obese PCOS group were significantly lower than those in the non-obese PCOS and control groups (p < 0.001). There was no statistically significant difference in the distribution of NUCB2 genotypes among the groups (p > 0.05), whereas nesfatin-1 levels in the CC and CG genotypes were lower than those in the GG genotype. Nesfatin-1 decreases in PCOS, especially in obese women, and is negatively correlated with cardiometabolic risk factors. Although genotype disturbances of NUCB2 were similar among the groups, CC and CG genotypes accompanied lower nesfatin-1 levels. C allele of NUCB2 gene polymorphism and nesfatin-1 may play a role in the pathophysiology of PCOS.

Mineralocorticoid receptor gene - 2G/C polymorphism in central serous chorioretinopathy and relation of polymorphism with plasma cortisol levels / 国际眼科杂志(Guoji Yanke Zazhi)

AIM:To evaluate the mineralocorticoid receptor ( MR) gene - 2G/ C single nucleotide polymorphism in central serous chorioretinopathy ( CSCR ), polymorphism and plasma cortisol level relationship. METHODS: Sixty CSCR patients and 50 controls were included in the study. Inclusion criteria for patients were acute manifestation of CSCR characterized by serous retinal detachment, RPE detachment or dysfunction without evidence of any other possible cause of fluid exudation, such as choroidal neovascularization, inflammation or infiltration. Peripheric blood sample was collected from the participants between 8 and 10 a. m. to avoid the diurnal changes of cortisol levels. MR (NR3C2) gene polymorphism ( rs2070951 ) and plasma cortisol levels sere studied. RESULTS: The genotype frequencies in CSCR group were G/ C (46. 6% ), G/ G (26. 7%) and C/ C (26. 7%). There was no statistically significant difference in terms of genotype distribution among groups ( P = 0. 96 ). The plasma cortisol levels were also studied and the results were 401. 2±162. 1 nmol/ L in the CSCR group and 296. 8±130. 1 nmol/ L in the control group and the difference was statistically significant ( P CONCLUSION: The MR (NR3C2) gene polymorphism is not associated with CSCR and the plasma cortisol levels.

Two different nucleotide substitutions of APC gene in a family with familial adenomatous polyposis.

Familial adenomatous polyposis (FAP) is an autosomal dominant syndrome leading to colorectal cancer. This disease appears as a result of germline mutation in adenomatous polyposis coli (APC) gene. The aim of the present study is to report the association between two different nucleotide substitutions detected in a family with FAP. In the proband, p.His1172Gln (c.3516delT) was detected in exon 15 of the APC gene. Furthermore, p.His1172Gln (c.3516delT) and, in addition to this mutation, p.Met1413Val (c.4237 A > G) were detected in exon 15 in both daughters of the proband. However, we believe that single nucleotide change in codon 1413 may be a polymorphic variant and deletion T in codon 1172 of APC gene is associated with FAP, attenuated FAP and extracolonic FAP involvement. Along with common use of genetic tests in the clinical practice, genotype-phenotype correlation may be recognized better and useful for early diagnosis and prevention of familial cancer syndromes.

The prevalence of 4G/5G polymorphism of plasminogen activator inhibitor-1 (PAI-1) gene in central serous chorioretinopathy and its association with plasma PAI-1 levels.

CONTEXT: Central serous chorioretinopathy (CSCR) is a poorly understood disease and the choroidal circulation abnormality induced by the plasminogen activator inhibitor type 1 (PAI-1) seems to be associated with the pathogenesis. There are many reports indicating that 4 G/5 G polymorphism of the PAI-1 gene is a risk factor for several diseases related to the elevated serum levels of PAI-1. OBJECTIVE: To evaluate the 4 G/5 G polymorphism of the PAI-1 gene and its association with serum levels of PAI-1 in acute CSCR patients. MATERIALS AND METHODS: Sixty CSCR patients and 50 healthy control patients were included. The PAI-1 4 G/5 G was genotyped using the polymerase chain reaction-restriction technique. Serum PAI-1 level was measured using enzyme-linked immunosorbent assay. Demographic data consisting of age, sex, body mass index (BMI) as well as genotype disturbances and serum PAI-1 levels were compared between the groups. Statistical significance for differences in the serum PAI-1 levels of each group with different genotypes was also analyzed. RESULTS: The CSCR group consisted of 40 male (66.7%) and 20 female (33.3%) patients with a mean age of 46.7 ± 8.39 years. The control group consisted of 32 male (64%) and 18 female (36%) healthy subjects with a mean age of 45.8 ± 8.39 years. There was no statistically significant difference between the groups in terms of age, sex and BMI. In the CSCR group the genotype frequencies were 4 G/4G: 30% (n = 18), 4G/5 G: 50% (n = 30), 5 G/5G: 20% (n = 12) and in the control group genotype frequencies were 34% (n = 17), 42% (n = 21) and 24% (n = 12), respectively. There was no statistically significant difference in the distribution of genotypes among the groups (chi-squared, p = 0.70). The CSCR group had a significantly higher serum PAI-1 concentration than the control group (p = 0.001). In both groups the mean plasma PAI-1 concentration did not vary significantly among the different genotypes (p > 0.05). DISCUSSION AND CONCLUSION: Although our results demonstrated that the patients with acute CSCR have higher serum PAI-1 concentrations than the controls, no significant difference was found in the genotype disturbances of the PAI-1 gene between the groups. The current study indicates that 4 G/5 G polymorphism in the promoter of the PAI-1 gene cannot be considered a risk factor for the elevated serum PAI-1 levels and consequent development of CSCR.

Association of the polymorphisms of vitamin D receptor and aggrecan genes with degenerative disc disease.

The aim of this study was to investigate the association between the polymorphisms of the vitamin D receptor (VDR) and aggrecan genes and degenerative disc disease in young Turkish patients. Aggrecan and VDR proteins are the main components of bone and cartilage. In our study, the polymorphisms of the VDR and aggrecan genes were investigated in a total of 300 individuals regarding disc degeneration and herniation. An association was found in the patients having VDR gene TT, Tt, FF, and Ff genotypes with the protrusion type of disc herniation, whereas the patients having tt and ff genotypes were associated with extrusion/sequestration types of the disease. Also, an association was observed between TT and FF genotypes of the VDR gene and mild forms of disc degeneration; and tt, ff, and Ff genotypes and severe forms of the disease. There was also an association between shorter, normal, and longer alleles of the aggrecan gene and a protrusion type of disc herniation. An association was found between short alleles and multilevel and severe disc degeneration, as well as normal and long alleles and mild disc degeneration. This study revealed that the polymorphisms of the VDR and aggrecan genes are associated with disc degeneration and herniation.

677C>T and 1298A>C polymorphisms of methylenetetrahydropholate reductase gene and biochemical parameters in Turkish population with spina bifida occulta.

AIM: This study aimed to investigate the 677C > T and 1298A > C MTHFR gene polymorphisms and their metabolic effects on the levels of folate, vitamin B12 and homocysteine in the serum of Turkish spina bifida occulta (SBO) patients and healthy individuals in disease. MATERIAL AND METHODS: A case-control study was performed to detect 677C > T and 1298A > C MTHFR gene polymorphisms in 39 SBO patients and 34 healthy individuals. The folate, vitamin B12 and homocysteine concentrations in the serum of SBO and healthy individuals were evaluated and compared with MTHFR gene polymorphisms. RESULTS: 677 CC/CT/TT MTHFR genotype frequency differences between the SBO patients and controls were not significant (x(2)=3.325, P=0.068; x(2)=1.479, P=0.224; x(2)=0.275, P=0.600; respectively). 1298A > C MTHFR genotype frequency differences between the SBO patients and controls were significant (x(2)=8.477, P=0.004). The frequencies of the Aand C alleles of the 1298A > C polymorphism did not differ in a statistically significant manner between the groups (x(2)=0.576, P=0.448). The biochemical parameters were not significantly different between SBO patients and healthy individuals (P > 0.05). CONCLUSION: The 677C > T and 1298A > C polymorphisms of the MTHFR gene cannot be regarded as major risk factors for SBO in the Turkish patients 677TT homozygosity may affect the metabolism of homocysteine.

Analysis of familial Mediterranean fever gene mutations in 202 patients with familial Mediterranean fever.

BACKGROUND: Familial Mediterranean fever (FMF) is an autosomal recessive disorder, caused by mutations in MEFV gene that encodes pyrin protein. In this study, we analyzed the most common five mutations in MEFV gene of 202 patients who were diagnosed formerly as FMF according to Tel-Hashomer criteria. The results of genetical analysis, clinical symptoms, and demographical aspects of those patients were evaluated retrospectively. METHODS AND RESULTS: Between the dates of February 2005 and March 2007, we analyzed five common MEFV gene mutations, which were M680I, M694V, M694I, V726A, and E148Q, in 202 patients by the PCR-ELISA method in our medical genetics laboratory. The most frequent mutation detected in our patients was M694V, and other mutations according to frequency were E148Q, M680I, V726A, and M694I. The detected mutations were homozygous in 45 of the patients (22.2%), heterozygous in 103 (51%), compound heterozygous in 52 (25.8%), and in 2 patients (1%) complex alleles were defined. The most common symptom was abdominal pain (80.4%) and other symptoms, respectively, were fever (57.8%), arthralgia (36.7%), chest pain (4.5%), and skin rash (2%). Amyloidosis was present in seven patients, and five of them had M694V mutation (homozygous), one of them had E148Q (heterozygous) mutation, and the other one had M694V/M694I mutation. CONCLUSION: In our patients, we defined 21 different genotypes of MEFV gene and the most common mutation was M694V. The most common symptoms were abdominal pain and fever. We detected significant correlation between the M694V, E148Q, and V726A mutations and clinical findings.

Genotyping for Cx26 and Cx30 mutations in cases with congenital hearing loss.

Hearing loss is the most frequent sensory defect in human being. The 13q11-q12 region contains the GJB2 and GJB6 genes, which code connexin 26 (CX26) and connexin 30 (CX30) proteins, respectively. The 35delG, 167delT, and 235delC mutations in the Cx26 gene are the main cause for sporadic nonsyndromic hearing loss (NSHL) in many populations. The 342-kb deletion [del(GJB6-D13S1830)] of the Cx30 gene is the second most common connexin mutation after the 35delG mutation in some NSHL populations. In our study 47 hearing-impaired students were included. The Cx26 gene and the Cx30 gene were analyzed for presence of the 35delG, 167delT, and 342-kb deletion [del(GJB6-D13S1830)]. Genotyping were performed for detecting 35delG, 167delT, and del(GJB6-D13S1830) mutations using the PCR-ELISA techniques. According to the results obtained from 47 cases, the 35delG mutation was detected in 7 cases ( approximately 14.9%). Four of these mutations were determined as homozygote mutant ( approximately 8.5%), and three were determined as heterozygote mutant ( approximately 6.4%). However, 167delT and del(GJB6-D13S1830) mutations were not detected in the study group. These results support the overwhelming majority of 35delG in our study group from deafness school in our study. In conclusion, the 35delG mutation was determined as the most frequently shown mutation that leads to congenital hearing loss as in previous studies from Turkey.

Intracerebral hematoma complicated with brain abscess in an infant. Case report.

A 45-day-old infant presented with a rare case of intracerebral hematoma complicated with brain abscess which developed after vitamin K deficiency. He was admitted to our emergency department with complaints of fever and confusion. Physical, neurological, and laboratory examinations and cranial computed tomography identified vitamin K deficiency and intracerebral hematoma. He started to suffer convulsions. The patient underwent surgery. A brain abscess was discovered with an intracerebral hematoma. The intracerebral hematoma and abscess were evacuated and antibiotic therapy was initiated. Convulsions became rare and were controlled with midozalam administration. Follow-up computed tomography after 6 months showed encephalomalacic changes in the temporoparietal area. If feeding depends only on human milk, the amount of vitamin K prophylaxis given to neonates should be increased to support vitamin K related factors.